Coronavirus infects and causes demyelination in primate central nervous system

Murray, Ronald S.; Cai, Guang-Yun; Hoel, Kristen; Zhang, J.-Y.; Soike, Kenneth F.; Cabirac, Gary F.

doi:10.1016/0042-6822(92)90757-g

Cited by 101 publications

(83 citation statements)

References 38 publications

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“…Some murine coronaviruses are neurotropic, neuroinvasive, and neurovirulent in rodents (27,58) and in nonhuman primates (11,38), inducing in some cases an MS-like demyelinating disease. Our goal is to investigate the possible neurotropism, neuroinvasion, and neurovirulence of the related HCoV, which have so far only been definitively associated with respiratory infections, with occasional reports of associations with diarrhea and neurologic diseases, mainly MS (39).…”

Section: Discussionmentioning

confidence: 99%

Neuroinvasion by Human Respiratory Coronaviruses

Arbour

Day

Newcombe

et al. 2000

J Virol

466

482

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Multiple sclerosis (MS) is a central nervous system (CNS) disease characterized by patches of demyelination and infiltration of inflammatory cells (21). The etiology of this disabling diseasehas not yet been determined, but both genetic factors, such as genes encoding human leukocyte antigens, T-cell receptors, and myelin basic protein (MBP) (18,19,26), and environmental factors such as viruses have been implicated (31). At least four human demyelinating diseases have a known viral etiology: subacute sclerosing panencephalitis as a late complication of measles virus infection of childhood (35), progressive multifocal leukoencephalopathy caused by the JC papovavirus (57), encephalopathy and myelopathy (neuro-AIDS) caused by human immunodeficiency virus (43), and human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (28). Over the last decades, several viruses have been associated with MS, based on detection of virions, viral nucleic acids, or viral proteins in CNS or the presence of antiviral antibodies in serum and/or cerebrospinal fluid. A confirmed association with MS is awaited but may involve more than one virus.Several studies have associated human coronaviruses (HCoV) with MS. Coronavirus-like particles were detected in autopsied brain tissue from an MS patient (56). Two coronaviruses that are molecularly related to murine neurotropic coronaviruses were isolated from brain material obtained at autopsy from two MS patients (9). Intrathecal anti-HCoV antibody synthesis indicative of a CNS infection was reported in MS patients (45). HCoV RNA was detected in MS patient brains (37, 51) and in cerebrospinal fluid of MS and other neurological disease (OND) patients (15). Coronavirus antigens were also detected in MS patient brains (37). Moreover, we have shown that HCoV can infect human astrocytes and microglia in primary cultures (8) and can acutely and persistently infect immortalized human glial cells (4, 5). Thus, accumulating evidence suggests that these viruses, first isolated as pathogens of the respiratory tract and now associated with up to one-third of human common colds (39), might be neurotropic, neuroinvasive, and neurovirulent in humans, as is the case for their murine counterpart, the coronavirus mouse hepatitis virus (MHV). Interestingly, upper respiratory infections of viral origin were shown to be an important trigger of MS attacks (2,40,48). Moreover, coronavirus seasonal patterns fit the observed occurrence of MS exacerbations (48).MHV-induced demyelinating disease involving coronaviruses is used as an animal model for elucidating the complex pathogenesis of MS. As for MS, MHV pathogenesis is multifactorial (27). Its outcome is influenced by genetics of the host and virus, dose and route of inoculation, and host age and immunological status at the time of infection (58). Neurotropic MHV strains could invade the CNS following an intranasal inoculation in mice (34) and could also gain access to the CNS via the hematogenous and/or lymphatic systems in mice (7) and i...

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Section: Discussionmentioning

confidence: 99%

Neuroinvasion by Human Respiratory Coronaviruses

Arbour

Day

Newcombe

et al. 2000

J Virol

466

482

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“…12,18,24 Primers used for amplification were as follows: complementary DNA (cDNA) synthesis (R1) 5Ј-ACGGACACCCAAAGTA-3Ј, upstream primer (R2) 5Ј-AGCACTTCTGTTTCCC-3Ј for picornavirus 25 ; cDNA synthesis (FAM1) 5Ј-CAGAGACTTGAAGATGTCTTTGC-3Ј, upstream primer (FAM2) 5Ј-GCTCTGTCCATGTTATTTG (GA)AT-3Ј for influenza virus type A 26,27 ; and cDNA synthesis (CVP3) 5Ј-IIAAATTGCTIITCTTGTTCTGGC-3Ј (I indicates inosine), downstream primer (CVP4) 5Ј-CCAAAATTCTGATTAGGGCCTCTC-3Ј for coronavirus OC43. 28 Complementary DNA was synthesized for 1 hour at 43°C in a reaction mix containing 10-mmol/L tromethamine hydrochloride (pH, . After an initial 4-minute heat denaturation at 94°C, 40 cycles of heat denaturation at 94°C for 1 minute, primer annealing at 49°C (picornavirus), 55°C (influenza virus type A), or 58°C (coronavirus) for 1 minute 30 seconds, and primer extension at 72°C for 1 minute were followed by a final primer extension step at 72°C.…”

Section: Reverse Transcription-polymerase Chain Reactionmentioning

confidence: 99%

Respiratory Tract Viral Infections in Inner-City Asthmatic Adults

Atmar¹,

Guy²,

Guntupalli³

et al. 1998

Arch Intern Med

200

151

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“…In this study we demonstrated that JHM virus estab-in mice, MHV persistent infections have also been detected in the rat and monkey CNS (27,28). lished a persistent infection within the retina of BALB/ c mice.…”

mentioning

confidence: 62%

Virus RNA Persists within the Retina in Coronavirus-Induced Retinopathy

et al. 1996

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The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. In the early phase, Day 1 to Day 7, a retinal vasculitis is noted which is associated with the presence of viral proteins and infectious virus. In the late phase, Day 10 to Day 140, a retinal degeneration is associated with the absence of viral proteins, infectious virus, and inflammatory cells. The purpose of this study was to determine if viral RNA persists within the retina during the retinal degenerative phase of the disease. BALB/c mice were inoculated by the intravitreal route with 10(4.0) TCID50/5 microliters of virus. The presence of viral RNA was detected by in situ hybridization with a viral cDNA probe and viral proteins were identified by immunocytochemical staining. During the acute phase of the infection, viral RNA was found in the retina, RPE, ciliary body epithelium, and the iris epithelium. During the late phase of the infection, viral RNA was almost exclusively found within the retina and RPE and not in the anterior segment of the eye. Within the retina, viral RNA was detected in the ganglion cell layer, the inner retina, the outer retina, and the RPE cell. Immunocytochemical staining identified viral protein within the retina only from Day 1 to Day 8. This ocular disease was also associated with a persistent systemic infection. Both viral RNA and viral proteins were identified within the liver during the first 8 days. However, only viral RNA was detected in the liver from Day 8 to Day 60. These studies demonstrate that MHV established an acute infection (Day 1-8) where infectious virus and viral proteins were identified. This was followed by a persistent infection within the retina and liver where only viral RNA were detected by in situ hybridization.

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Coronavirus infects and causes demyelination in primate central nervous system

Cited by 101 publications

References 38 publications

Neuroinvasion by Human Respiratory Coronaviruses

Neuroinvasion by Human Respiratory Coronaviruses

Respiratory Tract Viral Infections in Inner-City Asthmatic Adults

Virus RNA Persists within the Retina in Coronavirus-Induced Retinopathy

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